tbuckley/cabot-search huggingface dataset:
Abstract 13842: A Macromolecule-Linked Prodrug of Rapamycin Shows Potent Growth Inhibitory Effects Against Activated Fibroblasts Mimicking Fibroproliferative Transformation in Pulmonary Hypertension
Authors: Ivan S Alferiev, George Bratinov, David B Frank, Ilia Fishbein, Michael Chorny
Journal: Circulation (2023)

Introduction: Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive loss of vascular cell homeostasis with an irreversible shift toward the activated proliferative phenotype. New drug delivery approaches with improved efficacy are urgently needed for better clinical management of the disease. The present studies evaluated a novel prodrug-based strategy designed to durably suppress PH through enhanced delivery of rapamycin. We hypothesized that a long-circulating rapamycin prodrug constructed with a bioeliminable polyethylene glycol (PEG) scaffold would show efficacy as a new anti-PH drug candidate in cell culture and animal model studies. Methods: A new carrier-linked prodrug was synthesized by reversibly attaching rapamycin to 4-arm PEG (PEG-[RAPA] 4 , Mn = 40 kDa). Cell growth inhibitory effects of the construct were studied in vitro with proliferative fetal lung fibroblasts (HEL299) and transformed fibroblast-type cells (SK-LMS1), and in vivo using SK-LMS1 xenografts established in athymic nude mice. The results were analyzed by comparing the growth curve slopes (one-way ANOVA with the Tukey post hoc test). Results: Rapamycin (1-5 μM) potently inhibited proliferation of both fetal and transformed fibroblasts (75-95% inhibition 7 days post-treatment) in PDGF-BB-stimulated growth conditions (40 ng/ml, 2% FBS). Serum-stimulated (10% FBS) growth of both cell lines was also suppressed with remarkable potency at all tested concentrations (≥50% and ≥65% inhibition for HEL299 and SK-LMS1, respectively). In animal model studies, PEG-[RAPA] 4 given 2х/week strongly mitigated disease progression throughout the 4-week treatment period, whereas all animals in ‘no treatment’ and ‘blank PEG’ control groups were eliminated after reaching the end point. Statistical analysis confirmed markedly delayed growth of SK-LMS1 xenografts in the prodrug group (p = 0.032). Conclusions: Polymeric carrier-linked prodrug delivery of rapamycin effectively inhibits growth of activated fibroblasts in vitro and in a preclinical model recapitulating the altered vascular cell phenotype and proliferative character of the human disease. PEG-[RAPA] 4 is a promising candidate for further evaluation as a potential therapy for PH.
Abstract 19121: Averaged Impedance Drop Workflow for Pulmonary Vein Isolation
Authors: Daniel Friedman, Christopher Piorkowski, John H Tranter, Jed Overmann, Ilaaf Husain, Molly Speltz, Riki Thao, Jeffrey Fish
Journal: Circulation (2023)

Background: Previous studies demonstrate that averaged impedance drop (AID) is the most accurate predictor of focal atrial RF ablation lesion transmurality when using the TactiFlex™ SE Ablation Catheter in combination with AutoMark in EnSite™ X EP System version 3.0, however data demonstrating successful incorporation of AID into a pulmonary vein isolation workflow is lacking. Objective: We explored use of AID in conjunction with the AutoMark Distance (AMD) tool to create sets of contiguous, transmural atrial lesions in a chronic swine model and to compare results with inter-lesion gap rates from a historical study of a previous generation catheter (TactiCath) using LSI™ guidance. Methods: RSPV isolation and SVC-IVC and RSPV-CIPV lines were performed in swine (n=9) via point-by-point ablation (target contact force 10g). AID targets of 11, 13, and 15% were selected and minimum-maximum duration bounds were employed (30W/15-50s, 40W/8-20s and 50W/5-10s). Inter-lesion distances of 4mm and 5mm were chosen (balanced across RF powers and anatomical targets). After 12±3 days survival, lesion sets were examined using gross pathology and histology. Results: Histological analysis showed gap incidence rates of 4/223 (1.8%) and 9/215 (4.2%) in the right and left atria, respectively. Per-condition results are shown in Figure 1. The target AID was achieved in 339/487 (69.6%) of ablations, with the target AID reached prior to the minimum duration in 89/487 (18.3%) of trials. Collateral effects were observed, including pulmonary artery thrombosis and inflammation/necrosis extending to trachea/bronchus (N=1). Further characterization of these adverse events could potentially guide upper bounds for AID targets. Conclusions: AID guided ablation resulted in a low rate of inter-lesion gaps, overall comparable to historical data. However, safety and efficacy varied by delivery condition and these results may be useful for guiding clinical use.
Abstract 19150: DUSP1 is Associated With Map-Kinase Signaling in Antigen Presenting Cells Contributing to Salt-Sensitivity of Blood Pressure
Authors: Suha Arshad, Ashley Pitzer Mutchler, Mohammad Saleem, Lale A Ertuglu, Quanhu Sheng, Annet Kirabo
Journal: Circulation (2023)

Salt sensitivity of blood pressure, a pathological response characterized by a marked increase in blood pressure following salt intake, acts independently of hypertension as a risk factor for cardiovascular morbidities. Our recent research has elucidated a mechanism of sodium entry into antigen presenting cells through epithelial sodium channels (ENaC), which leads to the formation of neoantigen presenting isolevuglandin protein adducts via oxidative stress. Reactive oxygen species present in the cell may impact inflammation response as well as other intracellular pathways, chiefly the MAPK pathway. Previous studies have established an inhibitory connection between the protein-coding phosphatase DUSP1 and MAPKs. We hypothesize that DUSP1 acts as a negative regulator of MAPK signaling pathways involved in the immune response to salt-sensitive hypertension. To test our hypothesis, we isolated human monocytes from healthy participants (N=11) and treated them with either normal (150 mMol/L) or high (190 mMol/L) Na+ for 72 hours in vitro. Analysis of bulk RNA sequence data points to a significant upregulation of DUSP1 in the high salt environments compared to normal salt levels (4339 ± 770.1 vs 2721 ± 546.4 , p=0.0192). We also found that the high salt treatment led to increased expression of ERK1 (HS:2066 ± 184.0 NS:1560 ± 136.7 p= 0.0652), ERK2 (HS:8364 ± 669.8 NS:6256 ± 578.3 p= 0.0281), JNK (HS:1069 + 102.2 NS:792.3 ± 74.85 p= 0.0336), and p38 (HS: 4062 ± 329.0 NS:3010 ± 292.5, p= 0.0336). To study further, we enrolled 9 hypertensive participants who discontinued anti-hypertensive therapy for 2 weeks in an inpatient protocol to phenotype them through rapid salt loading and depletion. Blood pressure was recorded and blood collected at baseline, after salt loading, and after salt depletion and CITE-Seq analysis was performed on isolated PBMCs. After salt loading, we found a negative correlation between both p38 expression and pulse pressure (r= -0.7564 p= 0.0299) and p38 expression and systolic blood pressure (r= -0.8371, p=0.0095). We found a positive correlation between DUSP1 expression and systolic blood pressure after salt depletion (r= 0.7089, p=0.0490). These results suggest that DUSP1 plays an important role in salt sensitivity of blood pressure.
Abstract 16080: Complementary Roles of Near-Infrared Spectroscopy and Intravascular Ultrasound in the Prediction of Periprocedural Myocardial Injury
Authors: Daisuke Irie, Hidenari Matsumoto, Koji Isodono, Satoshi Higuchi, Hiroki Tanisawa, HIdefumi Ohya, Ryoji Kitamura, Toshiro Shinke
Journal: Circulation (2023)

[Introduction] Lipid-rich plaque detected by near-infrared spectroscopy (NIRS) and attenuated plaque detected by intravascular ultrasound (IVUS) predict periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI). The relationship between echolucent plaque detected by IVUS (considered to represent intraplaque hemorrhage) and PMI remains uncertain. [Research Questions] Can the combination of NIRS and IVUS enhance the prediction of PMI? [Aims] We aimed to elucidate whether echolucent plaque is independently associated with PMI following elective PCI and whether the combination of NIRS and IVUS signatures improves the predictive ability for PMI. [Methods] This multicenter retrospective study included 121 lesions from 121 patients who underwent elective NIRS-IVUS-guided stent implantation. PMI was defined as post-PCI cardiac troponin-T &amp;gt;5х the upper reference limit. A maximum 4-mm lipid core burden index &amp;gt;457 was regarded as lipid-rich plaque. Echolucent plaque and attenuated plaque were defined as the presence of an echolucent zone and an attenuation arc &amp;gt;90° on IVUS, respectively. [Results] PMI occurred in 39 lesions. Multivariable analysis revealed that echolucent plaque, attenuated plaque, and lipid-rich plaque were independent predictors of PMI. Adding echolucent plaque and attenuated plaque to lipid-rich plaque improved the predictive performance (C-statistics: 0.825 vs. 0.688; p=0.001). The incidence of PMI increased with the number of predictors: 3% (1/39), 29% (10/34), 47% (14/30), and 78% (14/18) for 0, 1, 2, and 3 predictors, respectively. [Conclusions] Echolucent plaque emerged as a significant predictor of PMI, independent of lipid-rich plaque and attenuated plaque. Compared with NIRS alone, the combination of NIRS with IVUS signatures improved the predictive ability of imaging.
Abstract 13836: Percentage of Patients Achieving Blood Pressure Goals With Aprocitentan, a Dual Endothelin Receptor Antagonist: Results From a Randomized, Controlled Phase 3 Study (PRECISION)
Authors: Michael A Weber, Jiguang Wang, John M Flack, Markus Schlaich, George Bakris, Wentao Lu, Lloyd Haskell, Krzysztof Narkiewicz
Journal: Circulation (2023)

Background: In the phase 3 PRECISION trial, aprocitentan (APRO) lowered BP in patients with resistant hypertension. Research Question: How effective is APRO for achieving the following BP goals over 4 weeks: mean 24-hour ambulatory BP monitoring (ABPM) measurements &lt;130/80 mmHg, daytime ABPM &lt;135/85 mmHg, nighttime ABPM &lt;120/70 mmHg, reduction in 24-hour ABPM ≥5 mmHg, mean trough unattended automated office BP &lt;130/80 mmHg, and reduction in office systolic BP (SBP) ≥10 mmHg? Aim: To evaluate percentages of patients achieving BP goals with APRO or placebo (PBO) after 4 weeks of treatment. Methods: Patients had sitting unattended automated office SBP ≥140 mmHg despite prescription of ≥3 antihypertensives of different classes in the year prior to enrollment. After 4 weeks of standardized triple therapy (amlodipine, valsartan, hydrochlorothiazide), those still hypertensive could enter a 4-week single-blind placebo (PBO) run-in period, followed by a 4-week double-blind period wherein patients were randomized 1:1:1 to APRO 12.5 mg, 25 mg, or PBO added to background therapy. We evaluated percentages of patients achieving BP goals during the double-blind period. Results: The APRO 12.5 mg, APRO 25 mg, and PBO groups comprised 243, 243, and 244 patients, respectively. Among 633 patients with ABPM data, 41.1%, 51.6%, and 29.6% in the APRO 12.5 mg, APRO 25 mg, and PBO groups had 24-hour mean ABPM &lt;130/80 mmHg. Similarly, 47.4%, 52.7%, and 35.8% in the APRO 12.5 mg, APRO 25 mg, and PBO groups had daytime ABPM &lt;135/85 mmHg; 37.9%, 44.0%, and 22.9%, respectively, had nighttime ABPM &lt;120/70 mmHg. In the APRO 12.5 mg, APRO 25 mg, and PBO groups, 61.7%, 64.8%, and 39.7% had reductions in ABPM of ≥5 mmHg. Overall, 25.1%, 24.2%, and 16.5% in the APRO 12.5 mg, APRO 25 mg, and PBO groups achieved mean office BP &lt;130/80 mmHg; 65.0%, 65.8%, and 55.8%, respectively, had reductions in office SBP of ≥10 mmHg. APRO was generally well tolerated. Edema or fluid retention occurred in 9%, 18%, and 2% of patients in the APRO 12.5 mg, 25 mg, and PBO groups, respectively, during the 4-week double-blind period. Conclusion: Greater proportions of patients receiving APRO versus PBO achieved BP goals at 4 weeks. Based on ABPM, treatment benefits with APRO showed dose-dependency, with a larger effect for APRO 25 mg.
Abstract 15611: Disparities in Hypertension Control Amidst the Pandemic: A Multi-Year Analysis Using Multiple Hospital Database
Authors: Olayiwola Bolaji, Shaumi Yun, Olanrewaju Adabale, Faizal Ouedraogo, Abiodun Idowu, Bede Nriagu, Endurance O Evbayekha, Habeeb Sanni, Stanley Oghoghorie, Revanth Reddy Bandaru, Arthur Dilibe, Osejie Oriaifo, Saeed Shoar
Journal: Circulation (2023)

Introduction: Hypertension, a pervasive global health concern, affects roughly half of US adults and can lead to serious health issues if uncontrolled. This study utilized the Epic Cosmos anonymized database to evaluate blood pressure (BP) control efficacy and related disparities among hypertensive patients from 196 healthcare institutions. Additionally, we explored the pandemic impact on these outcomes. Hypothesis: To evaluate blood pressure (BP) control efficacy and related disparities among hypertensive patients from 196 healthcare institutions using the Epic Cosmos anonymized database. Methods: Using the Epic Cosmos database, hypertension control rates from 2018 to 2022 were evaluated and stratified by patients' socio-demographic profiles. A multivariable logistic regression analysis identified factors associated with BP control rates. Results: In 2022, the study included 13.4 million hypertensive patients aged 18 and older. Of these, 66.0% achieved BP control (BP&lt; 140/90 mm Hg), 31.0% reached stricter control (BP&lt;130/80 mm Hg), and 7.0% had severely uncontrolled hypertension. Control rates were lower among Non-Hispanic Blacks (59.4%) compared to Non-Hispanic Whites (67.5%) with an adjusted odds ratio (AOR) of 0.749 (95% confidence interval (CI): 0.746-0.752). Self-pay patients were less likely to achieve control than insured patients (58.8% vs 66.8%, AOR: 0.79, 95% CI: 0.78-0.80). BP control rates fluctuated from 2018 to 2022, reflecting the pandemic's impact. Conclusions: The findings highlight suboptimal hypertension control rates and disparities in the US, emphasizing the need for tailored hypertension management initiatives. These should consider identified disparities and ensure accessibility and cultural sensitivity, aligning with the American Heart Association guidelines.
Abstract 13814: Combined Omental and Bilateral Pectoralis Major Flaps for Treatment of Thoracic Aortic Graft Infections
Authors: Kevin Kuonqui, David E Janhofer, Myles N LaValley, Sarah E Diaddigo, Hiroo Takayama, Jeffrey A Ascherman
Journal: Circulation (2023)

Introduction: Aortic graft infections have historically been managed through graft removal and replacement. However, coverage with vascularized tissue flaps may provide an effective alternative, particularly in patients who are not able to undergo extended extra-anatomic bypass procedures. Hypothesis: Here we describe our experience treating thoracic aortic graft infections with combined omental and bilateral pectoralis major myocutaneous (PMM) advancement flaps. Methods: All patients undergoing sternal wound treatment with PMM flaps by the senior author (JAA) at a high-volume cardiac surgery center from 1996-2023 were reviewed. Patients with evidence of aortic graft infection were included. Results: Complete data were available for 598 patients, 11 of whom had combined PMM and omental flaps mobilized for aortic graft infections. ASA score was &gt;4 in 9/11 (81.9%). At the index cardiac surgery, 11/11 (100%) underwent aortic root repair/replacement, and 9/11 (81.9%) also underwent aortic valve repair/replacement. Indications in this group for flap surgery included culture-positive infection (8/11; 72.7%), dehiscence (5/11; 45.5%), drainage (7/11; 63.6%), and inability to close the sternotomy incision due to hemodynamic instability (5/11; 45.5%). During chest exploration, 7/11 (63.6%) underwent complete removal of the infected graft, compared to 4/11 (36.4%) who underwent graft-preserving washout and debridement. Immediate flap closure was performed in 4/11 (36.4%). Intraoperative mediastinal cultures were positive in 3/11 (27.3%). Post-operative complications included dehiscence (1/11; 9.1%), seroma (2/11; 18.2%), hematoma (1/11, 9.1%), abdominal hernia (1/11; 9.1%), and recurrent infection (1/11; 9.1%). One (9.1%) patient died within 30 days of sternal reconstruction from mitral valve failure and a tachyarrhythmia. None have undergone reoperation for flap-related complications, while one patient underwent elective resection due to aesthetic complaints. Conclusions: Low postoperative morbidity and mortality indicate that combined omental and pectoralis major flaps are a safe and effective treatment for aortic graft infections.
Abstract 13890: Global Burden of Myocarditis From 1990 to 2019 and Projections Until 2030
Authors: Juying Qian, Ao Chen, Zhangwei Chen, Junbo Ge
Journal: Circulation (2023)

Introduction: Myocarditis remains a major public health challenge worldwide, which might be increasing with the pandemic of coronavirus disease 2019. This study aimed to examine the myocarditis burden at the global level, and predict the future trend until 2030. Methods: Incident cases, deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates, as metrics of myocarditis burden, were obtained from the Global Burden of Disease Study 2019. The estimated annual percentage changes (EAPCs) were calculated to reveal temporal trends from 1990 to 2019. Bayesian age-period-cohort model was used to make projections. Results: Increases were noted in incident cases (62.19%) and deaths (65.4%) of myocarditis, with a slight decrease of DALYs (-0.42%). Age-standardized death rate (ASDR) showed a stable trend over time [EAPC: -0.09, 95% confidence interval (CI): -0.38 to 0.2], decreases were noted in age-standardized incidence rate (ASIR) (EAPC: -0.23, 95% CI: -0.26 to -0.21) and age-standardized DALY rate (EAPC: -1.19, 95% CI: -1.33 to -1.04). Males bore more myocarditis burden than females. Almost a third (29.94%) of myocarditis patients resided in countries with a middle sociodemographic index (SDI). Higher ASIRs were observed in regions with higher SDI levels. People aged less than 20 years in low and low-middle SDI quintiles developed myocarditis and died from it earlier than those in other quintiles. Global ASIR and ASDR were predicted to continuously decrease until 2030. Conclusions: These findings suggested considerable heterogeneity in the epidemiologic patterns of myocarditis, guiding the policymakers to formulate optimal strategies and resource allocation for myocarditis.
Abstract 19189: A Rare Case of <i>Neisseria Gonorrhoeae</i> Native Aortic Valve Infective Endocarditis With Development of Gerbode Defect
Authors: Chris J Sidwell, Albert Ha, Alexandra Hua, Nicholas Pietrini, Brett Wanamaker, Bo Yang
Journal: Circulation (2023)

Introduction: Infective endocarditis (IE) is a devastating condition most commonly caused by gram-positive cocci ( S. aureus , S. viridans , S. gallolyticus , Enterococcus spp.) and gram-negative organisms (e.g. HACEK organisms). We present a case of Native Aortic Valve IE due to disseminated N. Gonorrhea in an immunocompetent patient. Hospital Course: The patient is a 30-year-old female who presented with a chief complaint of subacute chest pain and constitutional symptoms. Echocardiography revealed aortic valve abscess and severe aortic insufficiency with concerns of aorto-atrial fistula. The patient was treated with antibiotics and transferred to our hospital. Upon transfer, the patient was initially stable. Physical exam was notable for a pandiastolic murmur. The patient rapidly deteriorated into cardiogenic and septic shock. TTE revealed aortic root abscess, LVOT-RA fistula (Gerbode defect), and right atrial vegetation. Emergent surgical exploration revealed IE of the aortic valve with destruction of right and non-coronary cusps and vegetation eroding from the base of the aortic root through the membranous septum to the right atrium without tricuspid valve involvement. She underwent successful treatment with debridement and reconstruction. Initial blood cultures were positive for N. gonorrhoeae. The patient was negative for HIV and no gynecologic source was identified. After an extended hospital course, the patient was discharged with IV antibiotics. Discussion &amp; Conclusion: We present a rare case of N. Gonorrhoeae aortic valve endocarditis leading to aortic valve destruction with subsequent abscess and fistulae formation. This case demonstrates a rare and severe consequence of disseminated gonococcal infections (DGI), though the patient was without other manifestations of DGI.
Abstract 12502: Association Between Catheter Ablation and Dementia Among Patients With Atrial Fibrillation: A Meta-Analysis
Authors: Vikash Jaiswal, Song Peng Ang, Novonil Deb, Yusra Nasir, Poulami Roy, Kripa Rajak, Vagisha Sharma, Alisson Iturburu
Journal: Circulation (2023)

Background: Atrial fibrillation (AF) has been found to be associated with an increased risk of dementia. However, catheter ablation (CA) for AF might reduce the risk of dementia is unclear, with conflicting results till date. Objective: We aimed to evaluate the association between CA among AF patients and the incidence of Dementia. Methods: We performed a systematic literature search using the PubMed, Embase, Scopus, and Cochrane libraries for relevant articles from inception until 10th May 2023. Hazard ratios (HR) were pooled using a random-effect model, and a p-value of &lt;0.05 was considered statistically significant. Results: A total of 6 studies with 146709 patients (47040 in the AFCA group and 99669 in the non-CA group) were included in the study. The mean age of patients among CA and non-CA groups was comparable (58.7 vs. 58.18). The most common comorbidity among CA and non-CA groups was hypertension (30.30% vs.67.70%), respectively. Pooled analysis of primary outcome showed that CA significantly reduced the incidence of dementia (HR, 0.63(95%CI: 0.52-0.77), P&lt;0.001). Similarly, pooled analysis of secondary outcomes showed that the CA group of patients were having significantly reduced incidence of alzheimer's disease (HR, 0.78(95%CI: 0.66-0.92), P&lt;0.001) compared with the non-CA group. However, a non-statistically significant lower incidence of vascular dementia was observed in the AFCA group (HR, 0.63(95%CI: 0.38-1.06), P=0.08) compared with the non-CA group. Conclusion: Catheter ablation reduced the risk of dementia and alzheimer’s disease compared with the non-ablation group of patients.